It tells the story of Wallace, an artist/war hero/short order cook who saves a suicidal woman named Esther. She likes his art and they go out for a drink. They are ambushed by two men, who drug Wallace and kidnap Esther. Apparently, The Colonel and Liebowitz are a part of this conspiracy. Wallace spends the night in the drunk tank, after being dragged out of the gutter by two of Basin City's (notoriously corrupt) police officers, Manson and Bundy, and upon his release seeks out Esther. He is crossed once again by a squad of police officers after he tells Commissioner Liebowitz he plans to find Esther alone if need be, and proceeds to dispatch them with humiliating ease, leaving them bound, naked and without money. After locating Esther's home via his landlady, (she'd taken her address) he finds her apartment occupied by Delia, who claims to be Esther's roommate.

Wallace and Delia are attacked by The Colonel's new manservant, Manute, but they escape after Wallace beats him in hand-to-hand combat and defenestrates him (a reference to a similar scene from A Dame To Kill For). Then a sniper attacks from a nearby window, whom Wallace takes out by shooting him through the scope of his rifle, similar to a scene from RoboCop 2 (also written by Miller). All the while, Delia tries unsuccessfully to seduce him as they are pursued by two more assassins in a Mercedes, which Wallace also disposes of.

Afterwards, Wallace meets up with an old war buddy referred to only as Captain. He borrows an old Chevrolet Nomad known as The Heap from him and Wallace and Delia turn in for the night at the Last Hope Motel (a reference to Nancy Callahan's car and the place where she and John Hartigan hide in That Yellow Bastard).

Wallace handcuffs her to the bed for what she believes is foreplay, when he reveals that he knows she cannot be Esther's roommate, since Esther's clothes would have the smell of Delia's cigarettes on them. Just then, Wallace is drugged by a sniper for the second time. He wakes at the Santa Yolanda Tar Pits, where Delia, Gordo, and a drug wizard named Maxine are preparing to abandon his car in the pits. Maxine gives him a huge dose of something strange and Wallace goes on a trip.

They shoot past Delia, Maxine and Gordo at a gas station where they were refilling the Humvee they were driving. As they begin driving again, Wallace and Captain ambush them, with Captain disabling the Hummer with a rocket launcher. As they move in, Gordo mortally wounds Captain as Wallace shoots Gordo in the face. At gunpoint, Wallace makes Maxine bring him out of his hallucination hell. As she does, he shoots her in the head and shoots Delia through the gut when he suffers a panic attack. After blacking out for a few seconds, Wallace finds himself back in a black and white "normal" world, Maxine dead and Delia wounded. Paralyzed from the waist down, and genuinely fearful, she begs him to have mercy on her, and as a last act of chivalry Wallace does so by shooting her in the back of her head (she never sees what hits her). He then carries Captain's body back to the Heap and drives away.

He meets up with another war buddy named Jerry, the Captain's lover. They burn Captain's body in a funeral pyre, where afterwards they work trying to flush the rest of the drugs out of Wallace's system. Mariah, another female mercenary working for The Colonel, is assigned to Delia's task in her stead. The Colonel is now killing anyone linking Wallace to him, starting with the doctor who kidnapped Esther. He even has Mariah break Liebowitz's teenage son's arm after luring him away from his high school. He then threatens Liebowitz's family even further, putting the commissioner in a moral quandary.

Wallace confronts Liebowitz in his apartment and tries to get him to join his side. Wallace discovers that the real scheme The Colonel is operating is a slave trafficking and organ harvestingring of which Liebowitz was in fact (intentionally or otherwise) unaware of. Wallace explains how he launched a one-man assault on the factory, first infiltrating the complex, cutting a swathe of stealthy death through the roster of guards and discovering the myriad atrocities going on there. He was then confronted by Mariah and The Colonel as well as many, many armed guards. Wallace managed to escape the factory with his own life but without saving anyone, much to his own chagrin.

At this point, the phone rings in Liebowitz's apartment: "They know you're here", Liebowitz tells Wallace. It's The Colonel, telling Wallace where Esther is: she is at the Roark familyfarm, long since abandoned at this point. The deal is simple: Wallace's silence for Esther's safe return. When Wallace finds her, an enemy helicopter arrives and opens fire, Wallace shielding Esther with his body. However, Wallace is one step ahead: Jerry, who was up on a hill with heavy ordnance, blasts the chopper out of the sky with a rocket launcher; Wallace, who was wearing a Kevlar vest, survived the chopper's machinegun fire miraculously. Wallace takes Esther to the hospital and he and Jerry prepare to make a second assault on The Colonel's base of operations, when a flood of people are brought in on stretchers.

By this time, the police have launched a massive raid on The Colonel's factory, where The Colonel is captured. The Colonel threatens Liebowitz, who in return shoots him in the head for hurting his son and tells his underlings to "make a missing person outta the fucker". Wallenquist (the criminal lord behind the whole operation) lets it all be square, against the strong wishes of Mariah, (who somehow escaped the factory raid,) seeing neither power nor profit in revenge; He seeks revenge on neither Wallace nor Liebowitz.

Weeks later, Wallace and Esther leave town. He asks her why she wanted to jump and she responds "I was lonely". They drive away towards a better life away from Sin City.